Application of flow cytometry to molecular medicine: Detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts

  • Authors:
    • Alessandra Cappellini
    • Irina Mantovani
    • Pier Luigi Tazzari
    • Tiziana Grafone
    • Giovanni Martinelli
    • Lucio Cocco
    • Alberto M. Martelli
  • View Affiliations

  • Published online on: December 1, 2005     https://doi.org/10.3892/ijmm.16.6.1041
  • Pages: 1041-1048
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Abstract

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), a cytokine belonging to the TNF (tumor necrosis factor) family, is currently regarded as a potential anti-cancer agent. Nevertheless, several types of cancer cells display a low sensitivity to TRAIL or are completely resistant to this pro-apoptotic cytokine. TRAIL signalling is dependent on four receptors. Two of them, death receptors 4 and 5 (DR4 and DR5), induce apoptosis, whereas decoy receptors 1 and 2 (DcR1 and DcR2) are unable to evoke cell death upon TRAIL binding. TRAIL resistance may be related to the expression of TRAIL decoy receptors. TRAIL has been proposed as a novel therapeutic agent for the treatment of haematological disorders, including acute myeloid leukaemia (AML). Surprisingly, however, very limited information is available concerning the expression of TRAIL receptors in AML blasts. Here, we have evaluated, using flow cytometry, TRAIL receptor surface expression and sensitivity to TRAIL-dependent apoptosis of AML blasts from 30 patients. We observed frequent expression of TRAIL DcR1 and DcR2, while expression of DR4 and DR5 was less frequent. Nevertheless, the expression of DR4 or DR5 in leukaemic cells was always matched by a similar expression of one of the decoy receptors. Leukaemic blasts were invariably resistant, even to a high concentration (1000 ng/ml) of TRAIL. We suggest that AML blasts are resistant to TRAIL apoptosis in vitro. Therefore, it is unlikely that TRAIL alone might be used in the future as an innovative pharmacological agent for the treatment of AML.

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December 2005
Volume 16 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Cappellini A, Mantovani I, Tazzari PL, Grafone T, Martinelli G, Cocco L and Martelli AM: Application of flow cytometry to molecular medicine: Detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts. Int J Mol Med 16: 1041-1048, 2005
APA
Cappellini, A., Mantovani, I., Tazzari, P.L., Grafone, T., Martinelli, G., Cocco, L., & Martelli, A.M. (2005). Application of flow cytometry to molecular medicine: Detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts. International Journal of Molecular Medicine, 16, 1041-1048. https://doi.org/10.3892/ijmm.16.6.1041
MLA
Cappellini, A., Mantovani, I., Tazzari, P. L., Grafone, T., Martinelli, G., Cocco, L., Martelli, A. M."Application of flow cytometry to molecular medicine: Detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts". International Journal of Molecular Medicine 16.6 (2005): 1041-1048.
Chicago
Cappellini, A., Mantovani, I., Tazzari, P. L., Grafone, T., Martinelli, G., Cocco, L., Martelli, A. M."Application of flow cytometry to molecular medicine: Detection of tumor necrosis factor-related apoptosis-inducing ligand receptors in acute myeloid leukaemia blasts". International Journal of Molecular Medicine 16, no. 6 (2005): 1041-1048. https://doi.org/10.3892/ijmm.16.6.1041